BackgroundMultiple Endocrine Neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities.MethodsWe report on a cohort of MEN1 patients from the Groupe d'etude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totalling 262 families and 806 patients were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families.ResultsAccounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR=1.88: 95%-CI=1.15- 3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR=2.34; 95%-CI=1.23- 4.43).ConclusionThis genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up. [less ▲]

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in ... [more ▼]

ADAMTS (a disintegrin and metalloproteinase domain with thrombospondin motifs) constitute a family of endopeptidases related to matrix metalloproteinases. These proteases have been largely implicated in tissue remodeling and angiogenesis associated with physiological and pathological processes. To elucidate the in vivo functions of ADAMTS-12, we have generated a knockout mouse strain (Adamts12−/−) in which Adamts12 gene was deleted. The mutant mice had normal gestations and no apparent defects in growth, life span and fertility. By applying three different in vivo models of angiogenesis (malignant keratinocyte transplantation, Matrigel plug and aortic ring assays) to Adamts12−/− mice, we provide evidence for a protective effect of this host enzyme toward angiogenesis and cancer progression. In the absence of Adamts-12, both the angiogenic response and tumor invasion into host tissue were increased. Complementing results were obtained by using medium conditioned by cells overexpressing human ADAMTS-12, which inhibited vessel outgrowth in the aortic ring assay. This angioinhibitory effect of ADAMTS-12 was independent of its enzymatic activity as a mutated inactive form of the enzyme was similarly efficient in inhibiting endothelial cell sprouting in the aortic ring assay than the wild-type form. Altogether, our results show that ADAMTS-12 displays antiangiogenic properties and protect the host toward tumor progression. [less ▲]

We develop a new approach, based on quantization methods, to study higher symmetries of invariant di erential operators. We focus here on conformally invariant powers of the Laplacian over a conformally ... [more ▼]

We develop a new approach, based on quantization methods, to study higher symmetries of invariant di erential operators. We focus here on conformally invariant powers of the Laplacian over a conformally at manifold and recover results of Eastwood, Leistner, Gover and ilhan. In particular, conformally equivariant quantization establishes a correspondence between the algebra of Hamiltonian symmetries of the null geodesic ow and the algebra of higher symmetries of the conformal Laplacian. Combined with a symplectic reduction, this leads to a quantization of the minimal nilpotent coadjoint orbit of the conformal group. The star-deformation of its algebra of regular functions is isomorphic to the algebra of higher symmetries of the conformal Laplacian. Both identify with the quotient of the universal envelopping algebra by the Joseph ideal. [less ▲]

This paper singles out the key roles of US equity skewness and kurtosis in the hedge fund return generating process. We propose a conditional higher-moment model with location, trading, and higher-moment ... [more ▼]

This paper singles out the key roles of US equity skewness and kurtosis in the hedge fund return generating process. We propose a conditional higher-moment model with location, trading, and higher-moment factors to describe the dynamics of the equity hedge, event-driven, relative value, and fund of funds styles. If the volatility, skewness, and kurtosis implied in US options are used by fund managers as instruments to anticipate market movements, managers should adjust their market exposure in response to variations in these moments. We indeed show that higher-moment premia improve the conditional asset pricing model across all hedge fund styles. [less ▲]

The paper singles out the key roles of US equity skewness and kurtosis in the determination of the market premia embedded in Hedge Fund returns. We propose a conditional higher-moment asset pricing model ... [more ▼]

The paper singles out the key roles of US equity skewness and kurtosis in the determination of the market premia embedded in Hedge Fund returns. We propose a conditional higher-moment asset pricing model with location, trading and higher-moment factors in order to describe the dynamics of the Equity Hedge (Market Neutral, Short Selling and Long/Short strategies), Event Driven, Relative Value, and Funds of Hedge Funds styles. The volatility, skewness and kurtosis implied in the US options markets are used by Hedge Fund managers as instruments to anticipate market movements. Managers should adjust their market exposure in response to variations in the implied higher moments. We show that higher-moment premia improve a conditional asset pricing model both in terms of explanatory power (R-squares and Schwarz criterion) and specification errors across all Hedge Fund styles. [less ▲]

The reduced capacity of older skin to synthesize vitamin D(3) under the influence of ultraviolet light makes older persons at risk of vitamin D deficiency. The risk could even be increased in ... [more ▼]

The reduced capacity of older skin to synthesize vitamin D(3) under the influence of ultraviolet light makes older persons at risk of vitamin D deficiency. The risk could even be increased in institutionalized persons owing to their lower sunshine exposure. It has been reported that an inadequate vitamin D level is associated with secondary hyperparathyroidism, increased bone turnover, and bone loss, which increase fracture risk. The objective of this study was to assess the prevalence of inadequate serum vitamin D levels in institutionalized, postmenopausal, osteoporotic women. Assessment of 25-hydroxyvitamin D [25(OH)D] was performed in 445 institutionalized, osteoporotic women from nine countries (Australia, Belgium, France, Germany, Hungary, Italy, Poland, Spain and UK). For each institutionalized woman, three age-matched, noninstitutionalized, osteoporotic controls were also included. Four cutoffs of 25(OH)D inadequacy were fixed: less than 80, less than 75, less than 50 and less than 30 nmol/l. Mean age was 79.7 years (standard deviation [SD] = 5.8) for the institutionalized women and 79.5 years (SD = 5.5) for the noninstitutionalized women (p = 0.45). Significantly fewer institutionalized women received vitamin D supplements (13.2 vs 24.0%; p < 0.0001). In women without vitamin D supplements, the level of 25(OH)D was significantly lower in institutionalized women (56.9 [SD = 23.9] nmol/l) compared with noninstitutionalized women (63.2 [SD = 22.0] nmol/l; p < 0.0001). In institutionalized women (without vitamin D supplements), the prevalence of 25(OH)D inadequacy was 10.4, 41.2, 80.3 and 84.2% when considering cutoffs of 80, 75, 50 and 30 nmol/l, respectively. In the control group, the prevalence was 2.7, 22.9, 74.4 and 81.7%, respectively. The prevalence of vitamin D inadequacy was significantly higher in institutionalized women when considering the 75, 50 and 30 nmol/l cutoffs but not when considering the 80 nmol/l cutoff. This study highlights a high prevalence of vitamin D inadequacy in institutionalized, osteoporotic women. Compared with age-matched osteoporotic controls, the prevalence of severe vitamin D inadequacy was substantially more important in institutionalized women. We believe that a greater awareness of the importance of vitamin D inadequacy is needed in order to address this public health problem. [less ▲]

The histological assessment of atypical melanocytic neoplasms is mandatory to ensure proper diagnosis and treatment. However, for some atypical lesions, expert pathologists report only moderate ... [more ▼]

The histological assessment of atypical melanocytic neoplasms is mandatory to ensure proper diagnosis and treatment. However, for some atypical lesions, expert pathologists report only moderate concordance in the diagnosis. In addition, certain atypical neoplasms have been coined differently in the literature. These designations include among others atypical and metastasizing Spitz tumor, malignant Spitz naevus, borderline and intermediate melanocytic tumor, and melanocytic tumor of uncertain malignant potential (MELTUMP) or Spitzoid melanocytic tumor of uncertain malignant potential (STUMP). These neoplasms are grouped here under the heading melanocytoma. Such melanocytic lesions have a benign outcome but exhibit an atypical and worrisome aspect. Rare individual cases of melanocytomas can progress to locoregional disease (agminate melanocytomas), and even beyond. At times, the distinction between melanocytoma and melanoma is difficult and may even be impossible. However, multipronged immunohistochemistry can help define malignancy risk stratification and therapeutic guidelines. [less ▲]

The perifollicular and interfollicular areas of normal skin may look similar. However, some physiological and pathological processes may specifically involve a thin perifollicular rim. This review ... [more ▼]

The perifollicular and interfollicular areas of normal skin may look similar. However, some physiological and pathological processes may specifically involve a thin perifollicular rim. This review illustrates some of the methods available for highlighting the rim of the perifollicular epidermal unit. Non invasive methods rely on dermoscopy, ultraviolet light enhanced visualization (ULEV), skin capacitance imaging and cyanoacrylate skin surface strippings (CSSS). Conventional histology and immunohistochemistry may also show specific perifollicular features without, however, revealing the aspects highlighted by the specific non invasive methods. The clinically relevant modifications consist of pigmentary and hyperkeratotic perifollicular changes. [less ▲]

The Seventh European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ECCEO), which was held in Porto between March 28 and March 30, 2007, was the largest meeting in Europe in ... [more ▼]

The Seventh European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ECCEO), which was held in Porto between March 28 and March 30, 2007, was the largest meeting in Europe in the field of osteoporosis and osteoarthritis. The meeting was attended by similar to 4000 scientists and health professionals seeking information on the epidemiology, pathogenesis, prevention and treatment of osteoporosis and osteoarthritis. Specifically addressing these topics, > 500 abstracts were submitted. This paper highlights and summarises the important findings of ECCEO 2007. [less ▲]